The proposed work for next year will continue the two lines of investigation already underway. However, first priority on the work at this state is to establish cell lines with a requirement for retinoate or retinol for replication or normal differentiation. At least two of our cell lines appear to satisfy these criteria. We plan to determine the molecular step at which the retinoate is required. The other part of the proposed work is to determine that retinol is converted to retinoate somewhere in the body. If this can be proven directly, the site will be sought. If direct conversion cannot be found from either retinol or retinyl ester, conversion during absorption of beta-carotene will be studied. Our current working hypothesis is that retinol is converted to retinoate via retinaldehyde by intestinal wall enzymes.